Immunotherapy of Hormone-Refractory Prostate Cancer With Antigen-Loaded Dendritic Cells

2000 ◽  
Vol 18 (23) ◽  
pp. 3894-3903 ◽  
Author(s):  
Eric J. Small ◽  
Paige Fratesi ◽  
David M. Reese ◽  
George Strang ◽  
Reiner Laus ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Fusion Protein ◽  
Phase I ◽  
Phase Ii ◽  
Ex Vivo ◽  
Hormone Refractory Prostate Cancer ◽  
Tissue Antigen ◽  
Hormone Refractory

PURPOSE: Provenge (Dendreon Corp, Seattle, WA) is an immunotherapy product consisting of autologous dendritic cells loaded ex vivo with a recombinant fusion protein consisting of prostatic acid phosphatase (PAP) linked to granulocyte-macrophage colony-stimulating factor. Sequential phase I and phase II trials were performed to determine the safety and efficacy of Provenge and to assess its capacity to break immune tolerance to the normal tissue antigen PAP. PATIENTS AND METHODS: All patients had hormone-refractory prostate cancer. Dendritic-cell precursors were harvested by leukapheresis in weeks 0, 4, 8, and 24, loaded ex vivo with antigen for 2 days, and then infused intravenously over 30 minutes. Phase I patients received increasing doses of Provenge, and phase II patients received all the Provenge that could be prepared from a leukapheresis product. RESULTS: Patients tolerated treatment well. Fever, the most common adverse event, occurred after 15 infusions (14.7%). All patients developed immune responses to the recombinant fusion protein used to prepare Provenge, and 38% developed immune responses to PAP. Three patients had a more than 50% decline in prostate-specific antigen (PSA) level, and another three patients had 25% to 49% decreases in PSA. The time to disease progression correlated with development of an immune response to PAP and with the dose of dendritic cells received. CONCLUSION: Provenge is a novel immunotherapy agent that is safe and breaks tolerance to the tissue antigen PAP. Preliminary evidence for clinical efficacy warrants further exploration.

Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells: Results of a phase I clinical trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2551-2551
Author(s):  
A. Meye ◽  
S. Fuessel ◽  
M. Schmitz ◽  
S. Zastrow ◽  
C. Linne ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Dendritic Cells ◽  
T Cell ◽  
Phase I ◽  
T Cell Activation ◽  
T Cell Response ◽  
Phase I Clinical Trial ◽  
Hormone Refractory Prostate Cancer ◽  
Hormone Refractory

2551 Background: For patients with hormone-refractory prostate cancer (HRPC) treatment options are limited. Immunotherapies based on dendritic cells (DCs) might represent promising alternatives. In a Phase I clinical trial, we evaluated the safety and feasibility of a vaccination with monocyte-derived DCs loaded with a cocktail consisting of HLA-A*0201-restricted peptides derived from prostate cancer-associated antigens (PSA, PSMA, survivin, prostein, trp-p8). Methods: Eight HRPC patients were enrolled in this study (Table). Each patient underwent two leukaphereses, for the isolation of monocytes and subsequent generation of mature DCs. Patients received a total of four vaccinations each with peptide cocktail-loaded DCs at a dose of 1 x 107 cells both intradermally and intravenously every other week. Clinical response was monitored by the determination of the PSA level. The induction of a peptide-specific T-cell response was assessed by ELISPOT analysis. Results: Apart from local erythema and edema at the site of intradermal administration no side effects were noted. Four of eight patients showed a temporary PSA decline. One patient displayed a partial response with a PSA decrease > 50% for seven weeks and further stabilization for five weeks. Stable PSA values or decelerated PSA increases were observed in the three remaining patients. In ELISPOT analyses, three of four PSA responders also showed antigen-specific CD8+ T-cell activation against prostein, survivin and PSMA. Conclusions: The described protocol represents a safe and feasible concept for the induction of clinical and immunological responses. The application of a peptide cocktail derived from different antigens as a novel treatment modality is supposed to allow for the genetic and biologic heterogeneity of PCa. [Table: see text] [Table: see text]

Dose escalation phase of a phase I/II study of GTI-2501, an antisense to the R1 subunit of ribonucleotide reductase (RNR) and docetaxel in patients with metastatic hormone-refractory prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2078-2078 ◽  
Author(s):  
Y. Ko ◽  
S. North ◽  
S. R. Berry ◽  
D. S. Ernst ◽  
L. Klotz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Dose Escalation ◽  
Phase 1 ◽  
Single Agent ◽  
Pharmacokinetic Data ◽  
Hormone Refractory Prostate Cancer ◽  
Dose Cohort ◽  
Hormone Refractory

2078 Background: GTI-2501 (GTI) is a 20-mer oligonucleotide that is complementary to the R1 subunit of the RNR mRNA. The R1 protein is overexpressed in multiple tumour cell lines. GTI displays anti-tumour activity against prostate cancer xenografts in mice as a single agent and in combination with mitoxantrone. GTI also adds to the anti-tumour efficacy of taxanes in breast cancer xenografts in mice. A Phase 1 study of a 14 day continuous infusion of GTI in patients with solid tumours showed no dose limiting toxicities at doses up to 210.9 mg/m2/day. The objective of this dose escalation phase of a phase I/II study was to define a safe phase II dose of GTI in combination with docetaxel (D) in men with metastatic hormone refractory prostate cancer (HRPC). Methods: Men with metastatic HRPC were enrolled at 3 centres in Canada. GTI was given as a 14d continuous IV infusion every 21d with D IV infusion started 2 hrs prior to the end of the GTI infusion. Planned dose escalation cohorts are summarized in table . Results: 13 men were enrolled to the 3 cohorts. All patients are evaluable for toxicity. There was one possible DLT - an episode of grade 4 neutropenia reported at cycle 2 day 1 in the highest dose cohort - but the duration of neutropenia could not be confirmed. 3 additional patients were accrued to that cohort with no DLTs. The most common gr 3/4 toxicity was attributable to D (10 pts with Gr 3/4 neutropenia). The observed incidence of Gr 3/4 neutropenia was expected since patients had weekly CBCs. Only 1 patient had febrile neutropenia. 11 pts had fatigue (4 Gr 3) related to D and /or GTI. Other GTI attributable adverse events were Gr 1/2 including transient rises in transaminases and PTT. The pharmacokinetic data which is summarized in the table will be presented in full at the meeting. Conclusions: GTI can be given safely at its highest planned dose with standard doses of D. A Phase II evaluation of the GTI + D combination is planned for men with HRPC. [Table: see text] [Table: see text]

Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells: Results of a phase I clinical trial

The Prostate ◽  
2006 ◽  
Vol 66 (8) ◽  
pp. 811-821 ◽  
Author(s):  
Susanne Fuessel ◽  
Axel Meye ◽  
Marc Schmitz ◽  
Stefan Zastrow ◽  
Clemens Linné ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Dendritic Cells ◽  
Phase I ◽  
Cancer Patients ◽  
Phase I Clinical Trial ◽  
Hormone Refractory Prostate Cancer ◽  
Hormone Refractory

604: A Phase I Trial of Vaccination of Personalized Peptides for HLA-A2/A24 Positive Patients with Hormone-Refractory Prostate Cancer

2007 ◽  
Vol 177 (4S) ◽  
pp. 202-202
Author(s):  
Hirotsugu Uemura ◽  
Motoyoshi Tanaka ◽  
Shigeya Uejima ◽  
Takafumi Minami ◽  
Kiyohide Fujimoto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Phase I Trial ◽  
Hormone Refractory Prostate Cancer ◽  
Hormone Refractory

Lycopene for Advanced Hormone Refractory Prostate Cancer: A Prospective, Open Phase II Pilot Study

2009 ◽  
Vol 181 (3) ◽  
pp. 1098-1103 ◽  
Author(s):  
Carla Schwenke ◽  
Burkhard Ubrig ◽  
Petra Thürmann ◽  
Christian Eggersmann ◽  
Stephan Roth
Keyword(s):  
Prostate Cancer ◽  
Pilot Study ◽  
Phase Ii ◽  
Hormone Refractory Prostate Cancer ◽  
Open Phase ◽  
Hormone Refractory
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